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Creation of blood-brain barrier transparent artificial nanoparticles for the treatment of central nervous system diseases

Research Project

Project/Area Number 20J20737
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionHokkaido University

Principal Investigator

Abd Elwakil Mahmoud  北海道大学, 生命科学院, 特別研究員(PD)

Project Period (FY) 2020-04-24 – 2023-03-31
Project Status Declined (Fiscal Year 2022)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2022: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2021: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2020: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsmRNA drugs / ionizable polyesters / Gene Therapy / Organocatalysis / Lipid Nanoparticles / Lung diseases / Combinatorial chemistry / Immunotherapy / Biomaterials
Outline of Research at the Start

The general outline of my research includes three main principles
1. Directed evolution of nanocarriers for specific non liver gene delivery.
2. Establishment of rapid and robust screening method to enable in vivo reprogramming of specific cells or tissues on-demand.
3. Understand the biology of CNS delivery and discover the associated endogenous proteins.
Upon having a proof of concept for the previously mentioned concepts, we can introduce a new exciting era for nucleic acid therapeutics. Understanding of those three core principles we will lead to evolve a new field namely; Nanoinformatics.

Outline of Annual Research Achievements

During the past year I have developed a novel platform for mRNA delivery beyond the hepatocytes referred as to ionizable polyester/polyether RNA-Transporters (iPORT LNP). The key findings for the past year are:
1. Development of ionizable lipo-polyether RNA transporters (iPORTs) that are produced via the organocatalytic ring-opening polymerization of glycidylamine monomers using steroidal initiators. Interestingly, the tacticity of the iPORTs had a significant impact on in vitro and in vivo RNA delivery efficiency and tropism and this impact was dependent of monomeric structure. The top performing Estriol-GA05-30 iPORT LNPs elicited strong antitumor activity in a therapeutic, prophylactic model and were well-tolerated in mice. This technology is being filed as a patent through Hokkaido University. Additionally a manuscript has been submitted to JACS, Manuscript ID: ja-2022-017103).
2. Development of ionizable polyester RNA-Transporters LNP that selectively transfect splenocytes and lungs after systemic administration. The results of this project is being filed as a patent through Hokkaido University as well. Furthermore, a manuscript is being prepared for submission to publications.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Although we are at very hard times during COVID-19, my research projects were going very well and research output was really great because:
1. I have submitted two patents in one year.
2. Two manuscripts were prepared and are being submitted for publication in top tier scientific journals.

Strategy for Future Research Activity

In the coming year I plan to:
1. Apply my mRNA iPORT LNP technology for therapeutic application in lung diseases, cancer immunotherapy and infectious diseases vaccines such as COVID-19.
2. Extend my combinatorial chemistry for RNA delivery for other hard tissues such as bone and central nervous system.
3. Communicate my iPORT LNP technology with scientific community via attending international conferences and big pharmaceutical companies.

Report

(2 results)
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (2 results)

All 2021 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Engineered e-decalactone lipomers by-pass the liver to selectively in vivo deliver mRNA to the lungs without targeting ligands2021

    • Author(s)
      Elwakil A, Gao T, Isono T, Sato Y, Elewa Y, Satoh T, Harashima H,
    • Journal Title

      Mater Horizons

      Volume: 8 Issue: 8 Pages: 2251-2259

    • DOI

      10.1039/d1mh00185j

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Patent(Industrial Property Rights)] Engineered polyesters for mRNA delivery to the lungs2020

    • Inventor(s)
      佐藤敏文、磯野拓也、A.E.Mahmoud、佐藤悠介、原島秀吉
    • Industrial Property Rights Holder
      北海道大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

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Published: 2020-07-07   Modified: 2024-03-26  

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